We have previously identified autoantibodies of Beta2-adrenergic receptors in the sera of patients with allergic asthma, allergic rhinitis, cystic fibrosis as well as in one pre-allergy and three apparently normal individuals. Further studies have shown that the presencd of the autoantibodies in these subjects was associated with autonomic nervous system dysfunction. In this present proposal we plan to screen two specific patient populations (one from the NIH allergy Clinic, the second from Children's Hospital Allergy unit in Buffalo) for the presence of Beta-receptor autoantibodies utilizing the following as criteria for identification of autoantibodies to Beta-receptors: [125I] Protein A binding, inhibition of [125I]-iodohydroxybenz-ylpindolol binding to Beta-receptors and specific immunoprecipation of solubilized Beta-receptor molecules. Utilizing serum fractionation and specific anti-human immunoglobulin antibodies, we plan to determine the exact nature of the werum factors responsible for the Beta-receptor effects. Receptor specificity of the autoantibodies will be determined by ligand binding studies to and receptor immunoprecipation of solubilized Beta1 and Beat2-adrenergic receptors as well as solubilized Alpha-adrenergic, muscarinic and insulin receptors. In patients identified to have sera autoantibodies to Beta-receptors, correlations will be made with Alpha and Beta-adrenergic and muscarinic receptor responsiveness. Correlations will be attempted utilizing and cummulating data on Beta-receptor autoantibodies and the various types and severity of allergic respiratory diseases. Using anti-Beta-receptor monoclonal antibodies, the antigenic determinants on Beta-receptors will be elucidated and competive assays will be utilized to determine autoantibody recognition sites. A new assay for autoantibodies will be developed.